Apparatus for treating a tumor or the like and articles incorporating the apparatus for treatment of the tumor

ABSTRACT

An apparatus is provided for selectively destroying dividing cells in living tissue formed of dividing cells and non-dividing cells. The dividing cells contain polarizable intracellular members and during late anaphase or telophase, the dividing cells are connected to one another by a cleavage furrow. The apparatus includes insulated electrodes to be coupled to a generator for subjecting the living tissue to electric field conditions sufficient to cause movement of the polarizable intracellular members toward the cleavage furrow in response to a non-homogeneous electric field being induced in the dividing cells. The movement of the polarizable intracellular intracellular members towards the cleavage furrow causes the breakdown thereof which adversely impacts the multiplication of the dividing cells. Preferably, an intervening member is disposed between each insulated electrode and the skin surface and each intervening member includes a conductive “floating” plate that protects against the effects on the patient from a breakdown in the insulation of the electrode.

CROSS-REFERENCE RELATED APPLICATIONS

[0001] This application is a continuation-in-part application of U.S.patent application Ser. No. 10/285,313, filed Oct. 31, 2002 which is acontinuation-in-part application of U.S. patent application Ser. No.10/263,329, filed Oct. 2, 2002, both of which are hereby incorporated byreference in their entirety.

TECHNICAL FIELD

[0002] This invention concerns selective destruction of rapidly dividingcells in a localized area, and more particularly, to an apparatus andmethod for selectively destroying dividing cells by applying an electricfield having certain prescribed characteristics using an apparatus thatis configured to be complimentary to a specific body part.

BACKGROUND

[0003] All living organisms proliferate by cell division, including cellcultures, microorganisms (such as bacteria, mycoplasma, yeast, protozoa,and other single-celled organisms), fungi, algae, plant cells, etc.Dividing cells of organisms can be destroyed, or their proliferationcontrolled, by methods that are based on the sensitivity of the dividingcells of these organisms to certain agents. For example, certainantibiotics stop the multiplication process of bacteria.

[0004] The process of eukaryotic cell division is called “mitosis”,which involves nice distinct phases (see Darnell et al., Molecular CellBiology, New York: Scientific American Books, 1986, p. 149). Duringinterphase, the cell replicates chromosomal DNA, which begins condensingin early prophase. At this point, centrioles (each cell contains 2)begin moving towards opposite poles of the cell. In middle prophase,each chromosome is composed of duplicate chromatids. Microtubularspindles radiate from regions adjacent to the centrioles, which arecloser to their poles. By late prophase, the centrioles have reached thepoles, and some spindle fibers extend to the center of the cell, whileothers extend from the poles to the chromatids. The cells then move intometaphase, when the chromosomes move toward the equator of the cell andalign in the equatorial plane. Next is early anaphase, during which timedaughter chromatids separate from each other at the equator by movingalong the spindle fibers toward a centromere at opposite poles. The cellbegins to elongate along the axis of the pole; the pole-to-pole spindlesalso elongate. Late anaphase occurs when the daughter chromosomes (asthey are not called) each reach their respective opposite poles. At thispoint, cytokinesis begins as the cleavage furrow begins to form at theequator of the cell. In other words, late anaphase is the point at whichpinching the cell membrane begins. During telophase, cytokinesis isnearly complete and spindles disappear. Only a relatively narrowmembrane connection joins the two cytoplasms. Finally, the membranesseparate fully, cytokinesis is complete and the cell returns tointerphase.

[0005] In meisosis, the cell undergoes a second division, involvingseparation of sister chromosomes to opposite poles of the cell alongspindle fibers, followed by formation of a cleavage furrow and celldivision. However, this division is not preceded by chromosomereplication, yielding a haploid germ cell.

[0006] Bacteria also divide by chromosome replication, followed by cellseparation. However, since the daughter chromosomes separate byattachment to membrane components; there is no visible apparatus thatcontributes to cell division as in eukaryotic cells.

[0007] It is well known that tumors, particularly malignant or canceroustumors, grow uncontrollably compared to normal tissue. Such expeditedgrowth enables tumors to occupy an ever-increasing space and to damageor destroy tissue adjacent thereto. Furthermore, certain cancers arecharacterized by an ability to transmit cancerous “seeds”, includingsingle cells or small cell clusters (metastasises), to new locationswhere the messastatic cancer cells grow into additional tumors.

[0008] The rapid growth of tumors, in general, and malignant tumors inparticular, as described above, is the result of relatively frequentcell division or multiplication of these cells compared to normal tissuecells. The distinguishably frequent cell division of cancer cells is thebasis for the effectiveness of existing cancer treatments, e.g.,irradiation therapy and the use of various chemo-therapeutic agents.Such treatments are based on the fact that cells undergoing division aremore sensitive to radiation and chemo-therapeutic agents thannon-dividing cells. Because tumors cells divide much more frequentlythan normal cells, it is possible, to a certain extent, to selectivelydamage or destroy tumor cells by radiation therapy and/or chemotherapy.The actual sensitivity of cells to radiation, therapeutic agents, etc.,is also dependent on specific characteristics of different types ofnormal or malignant cell types. Thus, unfortunately, the sensitivity oftumor cells is not sufficiently higher than that many types of normaltissues. This diminishes the ability to distinguish between tumor cellsand normal cells, and therefore, existing cancer treatments typicallycause significant damage to normal tissues, thus limiting thetherapeutic effectiveness of such treatments. Furthermore, theinevitable damage to other tissue renders treatments very traumatic tothe patients and, often, patients are unable to recover from a seeminglysuccessful treatment. Also, certain types of tumors are not sensitive atall to existing methods of treatment.

[0009] There are also other methods for destroying cells that do notrely on radiation therapy or chemotherapy alone. For example, ultrasonicand electrical methods for destroying tumor cells can be used inaddition to or instead of conventional treatments. Electric fields andcurrents have been used for medical purposes for many years. The mostcommon is the generation of electric currents in a human or animal bodyby application of an electric field by means of a pair of conductiveelectrodes between which a potential difference is maintained. Theseelectric currents are used either to exert their specific effects, i.e.,to stimulate excitable tissue, or to generate heat by flowing in thebody since it acts as a resistor. Examples of the first type ofapplication include the following: cardiac defibrillators, peripheralnerve and muscle stimulators, brain stimulators, etc. Currents are usedfor heating, for example, in devices for tumor ablation, ablation ofmalfunctioning cardiac or brain tissue, cauterization, relaxation ofmuscle rheumatic pain and other pain, etc.

[0010] Another use of electric fields for medical purposes involves theutilization of high frequency oscillating fields transmitted from asource that emits an electric wave, such as an RF wave or a microwavesource that is directed at the part of the body that is of interest(i.e., target). In these instances, there is no electric energyconduction between the source and the body; but rather, the energy istransmitted to the body by radiation or induction. More specifically,the electric energy generated by the source reaches the vicinity of thebody via a conductor and is transmitted from it through air or someother electric insulating material to the human body.

[0011] In a conventional electrical method, electrical current isdelivered to a region of the target tissue using electrodes that areplaced in contact with the body of the patient. The applied electricalcurrent destroys substantially all cells in the vicinity of the targettissue. Thus, this type of electrical method does not discriminatebetween different types of cells within the target tissue and results inthe destruction of both tumor cells and normal cells.

[0012] Electric fields that can be used in medical applications can thusbe separated generally into two different modes. In the first mode, theelectric fields are applied to the body or tissues by means ofconducting electrodes. These electric fields can be separated into twotypes, namely (1) steady fields or fields that change at relatively slowrates, and alternating fields of low frequencies that inducecorresponding electric currents in the body or tissues, and (2) highfrequency alternating fields (above 1 MHz) applied to the body by meansof the conducting electrodes. In the second mode, the electric fieldsare high frequency alternating fields applied to the body by means ofinsulated electrodes.

[0013] The first type of electric field is used, for example, tostimulate nerves and muscles, pace the heart, etc. In fact, such fieldsare used in nature to propagate signals in nerve and muscle fibers,central nervous system (CNS), heart, etc. The recording of such naturalfields is the basis for the ECG, EEG, EMG, ERG, etc. The field strengthin these applications, assuming a medium of homogenous electricproperties, is simply the voltage applied to the stimulating/recordingelectrodes divided by the distance between them. These currents can becalculated by Ohm's law and can have dangerous stimulatory effects onthe heart and CNS and can result in potentially harmful ionconcentration changes. Also, if the currents are strong enough, they cancause excessive heating in the tissues. This heating can be calculatedby the power dissipated in the tissue (the product of the voltage andthe current).

[0014] When such electric fields and currents are alternating, theirstimulatory power, on nerve, muscle, etc., is an inverse function of thefrequency. At frequencies above 1-10 KHz, the stimulation power of thefields approaches zero. This limitation is due to the fact thatexcitation induced by electric stimulation is normally mediated bymembrane potential changes, the rate of which is limited by the RCproperties (time constants on the order of 1 ms) of the membrane.

[0015] Regardless of the frequency, when such current inducing fieldsare applied, they are associated with harmful side effects caused bycurrents. For example, one negative effect is the changes in ionicconcentration in the various “compartments” within the system, and theharmful products of the electrolysis taking place at the electrodes, orthe medium in which the tissues are imbedded. The changes in ionconcentrations occur whenever the system includes two or morecompartments between which the organism maintains ion concentrationdifferences. For example, for most tissues, [Ca⁺⁺] in the extracellularfluid is about 2×10⁻³ M, while in the cytoplasm of typical cells itsconcentration can be as low as 10⁻⁷ M. A current induced in such asystem by a pair of electrodes, flows in part from the extracellularfluid into the cells and out again into the extracellular medium. About2% of the current flowing into the cells is carried by the Ca⁺⁺ ions. Incontrast, because the concentration of intracellular Ca⁺⁺ is muchsmaller, only a negligible fraction of the currents that exits the cellsis carried by these ions. Thus, Ca⁺⁺ ions accumulate in the cells suchthat their concentrations in the cells increases, while theconcentration in the extracellular compartment may decrease. Theseeffects are observed for both DC and alternating currents (AC). The rateof accumulation of the ions depends on the current intensity ionmobilities, membrane ion conductance, etc. An increase in [Ca⁺⁺] isharmful to most cells and if sufficiently high will lead to thedestruction of the cells. Similar considerations apply to other ions. Inview of the above observations, long term current application to livingorganisms or tissues can result in significant damage. Another majorproblem that is associated with such electric fields, is due to theelectrolysis process that takes place at the electrode surfaces. Herecharges are transferred between the metal (electrons) and theelectrolytic solution (ions) such that charged active radicals areformed. These can cause significant damage to organic molecules,especially macromolecules and thus damage the living cells and tissues.

[0016] In contrast, when high frequency electric fields, above 1 MHz andusually in practice in the range of GHz, are induced in tissues by meansof insulated electrodes, the situation is quite different. These type offields generate only capacitive or displacement currents, rather thanthe conventional charge conducting currents. Under the effect of thistype of field, living tissues behave mostly according to theirdielectric properties rather than their electric conductive properties.Therefore, the dominant field effect is that due to dielectric lossesand heating. Thus, it is widely accepted that in practice, themeaningful effects of such fields on living organisms, are only thosedue to their heating effects, i.e., due to dielectric losses.

[0017] In U.S. Pat. No. 6,043,066 ('066) to Mangano, a method and deviceare presented which enable discrete objects having a conducting innercore, surrounded by a dielectric membrane to be selectively inactivatedby electric fields via irreversible breakdown of their dielectricmembrane. One potential application for this is in the selection andpurging of certain biological cells in a suspension. According to the'066 patent, an electric field is applied for targeting selected cellsto cause breakdown of the dielectric membranes of these tumor cells,while purportedly not adversely affecting other desired subpopulationsof cells. The cells are selected on the basis of intrinsic or induceddifferences in a characteristic electroporation threshold. Thedifferences in this threshold can depend upon a number of parameters,including the difference in cell size.

[0018] The method of the '066 patent is therefore based on theassumption that the electroporation threshold of tumor cells issufficiently distinguishable from that of normal cells because ofdifferences in cell size and differences in the dielectric properties ofthe cell membranes. Based upon this assumption, the larger size of manytypes of tumor cells makes these cells more susceptible toelectroporation and thus, it may be possible to selectively damage onlythe larger tumor cell membranes by applying an appropriate electricfield. One disadvantage of this method is that the ability todiscriminate is highly dependent upon cell type, for example, the sizedifference between normal cells and tumor cells is significant only incertain types of cells. Another drawback of this method is that thevoltages which are applied can damage some of the normal cells and maynot damage all of the tumor cells because the differences in size andmembrane dielectric properties are largely statistical and the actualcell geometries and dielectric properties can vary significantly.

[0019] What is needed in the art and has heretofore not been availableis an apparatus for destroying dividing cells, wherein the apparatusbetter discriminates between dividing cells, including single-celledorganisms, and non-dividing cells and is capable of selectivelydestroying the dividing cells or organisms with substantially no affecton the non-dividing cells or organisms and which can be configured toapplied to a specific body part, such as an extremity and thus lendsitself to being incorporated into an article of clothing.

SUMMARY

[0020] An apparatus for use in a number of different applications forselectively destroying cells undergoing growth and division is provided.This includes, cell, particularly tumor cells, in living tissue andsingle-celled organisms. The apparatus can be incorporated into a numberof different configurations that are specifically designed to beeffective for specific body parts so that the apparatus distinctlytargets a localized area to eliminate or control the growth of suchliving tissue or organisms. For example and as will be described ingreater detail hereinafter, the apparatus is particularly capable ofbeing incorporated into a piece of clothing that is worn over the tumorarea. One of the configurations of the apparatus is in the form of ahat, cap or other type of structure to be fitted over a person's headfor treating intra-cranial tumors, external scalp lesions or otherlesions. In another configuration, the apparatus is in the form of amodified bra or the like to be fitted over breasts for treating breastcancer or other type of tumor condition. In addition, the apparatus canbe incorporated into clothing that is to be worn over other body parts,such as testicles, a hand, leg, arm, neck, etc., for treating alocalized tumor in one of these locations (body parts). For example, ahigh standing collar member or necklace type structure can be used totreat thyroid, parathyroid, laryngeal lesions, etc. In this embodiment,the apparatus (either completely or partially) is disposed withinclothing that is fit around the neck for treating these conditions. Inanother aspect, localized treatment is provided by the apparatus when itis in the form of an internal member (e.g., a probe or catheter) that isinserted into the body through a natural pathway, such as the urethra,vagina, etc., or the member can penetrate the skin to and other tissuesto reach an internal target.

[0021] A major use of the present apparatus is in the treatment oftumors by selective destruction of tumor cells with substantially noaffect on normal tissue cells, and thus, the exemplary apparatus isdescribed below in the context of selective destruction of tumor cells.It should be appreciated however, that for purpose of the followingdescription, the term “cell” may also refer to a single-celled organism(eubacteria, bacteria, yeast, protozoa), multi-celled organisms (fungi,algae, mold), and plants as or parts thereof that are not normallyclassified as “cells”. The exemplary apparatus enables selectivedestruction of cells undergoing division in a way that is more effectiveand more accurate (e.g., more adaptable to be aimed at specific targets)than existing methods. Further, the present apparatus causes minimaldamage, if any, to normal tissue and, thus, reduces or eliminates manyside-effects associated with existing selective destruction methods,such as radiation therapy and chemotherapy. The selective destruction ofdividing cells using the present apparatus does not depend on thesensitivity of the cells to chemical agents or radiation. Instead, theselective destruction of dividing cells is based on distinguishablegeometrical characteristics of cells undergoing division, in comparisonto non-dividing cells, regardless of the cell geometry of the type ofcells being treated.

[0022] According to one exemplary embodiment, cell geometry-dependentselective destruction of living tissue is performed by inducing anon-homogenous electric field in the cells using an electronicapparatus.

[0023] It has been observed by the present inventor that, whiledifferent cells in their non-dividing state may have different shapes,e.g., spherical, ellipsoidal, cylindrical, “pancake-like”, etc., thedivision process of practically all cells is characterized bydevelopment of a “cleavage furrow” in late anaphase and telophase. Thiscleavage furrow is a slow constriction of the cell membrane (between thetwo sets of daughter chromosomes) which appears microscopically as agrowing cleft (e.g., a groove or notch) that gradually separates thecell into two new cells. During the division process, there is atransient period (telophase) during which the cell structure isbasically that of two sub-cells interconnected by a narrow “bridge”formed of the cell material. The division process is completed when the“bridge” between the two sub-cells is broken. The selective destructionof tumor cells using the present electronic apparatus utilizes thisunique geometrical feature of dividing cells.

[0024] When a cell or a group of cells are under natural conditions orenvironment, i.e., part of a living tissue, they are disposed surroundedby a conductive environment consisting mostly of an electrolyticinter-cellular fluid and other cells that are composed mostly of anelectrolytic intra-cellular liquid. When an electric field is induced inthe living tissue, by applying an electric potential across the tissue,an electric field is formed in the tissue and the specific distributionand configuration of the electric field lines defines the direction ofcharge displacement, or paths of electric currents in the tissue, ifcurrents are in fact induced in the tissue. The distribution andconfiguration of the electric field is dependent on various parametersof the tissue, including the geometry and the electric properties of thedifferent tissue components, and the relative conductivities, capacitiesand dielectric constants (that may be frequency dependent) of the tissuecomponents.

[0025] The electric current flow pattern for cells undergoing divisionis very different and unique as compared to non-dividing cells. Suchcells including first and second sub-cells, namely an “original” celland a newly formed cell, that are connected by a cytoplasm “bridge” or“neck”. The currents penetrate the first sub-cell through part of themembrane (“the current source pole”); however, they do not exit thefirst sub-cell through a portion of its membrane closer to the oppositepole (“the current sink pole”). Instead, the lines of current flowconverge at the neck or cytoplasm bridge, whereby the density of thecurrent flow lines is greatly increased. A corresponding, “mirrorimage”, process that takes place in the second sub-cell, whereby thecurrent flow lines diverge to a lower density configuration as theydepart from the bridge, and finally exit the second sub-cell from a partof its membrane closes to the current sink.

[0026] When a polarizable object is placed in a non-uniform convergingor diverging field, electric forces act on it and pull it towards thehigher density electric field lines. In the case of dividing cell,electric forces are exerted in the direction of the cytoplasm bridgebetween the two cells. Since all intercellular organelles andmacromolecules are polarizable, they are all force towards the bridgebetween the two cells. The field polarity is irrelevant to the directionof the force and, therefore, an alternating electric having specificproperties can be used to produce substantially the same effect. It willalso be appreciated that the concentrated and inhomogeneous electricfield present in or near the bridge or neck portion in itself exertsstrong forces on charges and natural dipoles and can lead to thedisruption of structures associated with these members.

[0027] The movement of the cellular organelles towards the bridgedisrupts the cell structure and results in increased pressure in thevicinity of the connecting bridge membrane. This pressure of theorganelles on the bridge membrane is expected to break the bridgemembrane and, thus, it is expected that the dividing cell will “explode”in response to this pressure. The ability to break the membrane anddisrupt other cell structures can be enhanced by applying a pulsatingalternating electric field that has a frequency from about 50 KHz toabout 500 KHz. When this type of electric field is applied to thetissue, the forces exerted on the intercellular organelles have a“hammering” effect, whereby force pulses (or beats) are applied to theorganelles numerous times per second, enhancing the movement oforganelles of different sizes and masses towards the bridge (or neck)portion from both of the sub-cells, thereby increasing the probabilityof breaking the cell membrane at the bridge portion. The forces exertedon the intracellular organelles also affect the organelles themselvesand may collapse or break the organelles.

[0028] According to one exemplary embodiment, the apparatus for applyingthe electric field is an electronic apparatus that generates the desiredelectric signals in the shape of waveforms or trains of pulses. Theelectronic apparatus includes a generator that generates an alternatingvoltage waveform at frequencies in the range from about 50 KHz to about500 KHz. The generator is operatively connected to conductive leadswhich are connected at their other ends to insulatedconductors/electrodes (also referred to as isolects) that are activatedby the generated waveforms. The insulated electrodes consist of aconductor in contact with a dielectric (insulating layer) that is incontact with the conductive tissue, thus forming a capacitor. Theelectric fields that are generated by the present apparatus can beapplied in several different modes depending upon the precise treatmentapplication.

[0029] In one exemplary embodiment, the electric fields are applied byexternal insulated electrodes which are incorporated into an article ofclothing and which are constructed so that the applied electric fieldsare of a local type that target a specific, localized area of tissue(e.g., a tumor). This embodiment is designed to treat tumors and lesionsthat are at or below the skin surface by wearing the article of clothingover the target tissue so that the electric fields generated by theinsulated electrodes are directed at the tumors (lesions, etc.).

[0030] According to another embodiment, the apparatus is used in aninternal type application in that the insulated electrodes are in theform of a probe or catheter etc., that enter the body through naturalpathways, such as the urethra or vagina, or are configured to penetrateliving tissue, until the insulated electrodes are positioned near theinternal target area (e.g., an internal tumor).

[0031] Thus, the present apparatus utilizes electric fields that fallinto a special intermediate category relative to previous high and lowfrequency applications in that the present electric fields arebio-effective fields that have no meaningful stimulatory effects and nothermal effects. Advantageously, when non-dividing cells are subjectedto these electric fields, there is no effect on the cells; however, thesituation is much different when dividing cells are subjected to thepresent electric fields. Thus, the present electronic apparatus and thegenerated electric fields target dividing cells, such as tumors or thelike, and do not target non-dividing cells that is found around inhealthy tissue surrounding the target area. Furthermore, since thepresent apparatus utilizes insulated electrodes, the above mentionednegative effects, obtained when conductive electrodes are used, i.e.,ion concentration changes in the cells and the formation of harmfulagents by electrolysis, do not occur with the present apparatus. This isbecause, in general, no actual transfer of charges takes place betweenthe electrodes and the medium, and there is no charge flow in the mediumwhere the currents are capacitive.

[0032] It should be appreciated that the present electronic apparatuscan also be used in applications other than treatment of tumors in theliving body. In fact, the selective destruction utilizing the presentapparatus can be used in conjunction with any organism that proliferatesdivision and multiplication, for example, tissue cultures,microorganisms, such as bacteria, mycoplasma, protozoa, fungi, algae,plant cells, etc. Such organisms divide by the formation of a groove orcleft as described above. As the groove or cleft deepens, a narrowbridge is formed between the two parts of the organism, similar to thebridge formed between the sub-cells of dividing animal cells. Since suchorganisms are covered by a membrane having a relatively low electricconductivity, similar to an animal cell membrane described above, theelectric field lines in a dividing organism converge at the bridgeconnecting the two parts of the dividing organism. The converging fieldlines result in electric forces that displace polarizable elements andcharges within the dividing organism.

[0033] The above, and other objects, features and advantages of thepresent apparatus will become apparent from the following descriptionread in conjunction with the accompanying drawings, in which likereference numerals designate the same elements.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0034] FIGS. 1A-1E are simplified, schematic, cross-sectional,illustrations of various stages of a cell division process;

[0035]FIGS. 2A and 2B are schematic illustrations of a non-dividing cellbeing subjected to an electric field;

[0036]FIGS. 3A, 3B and 3C are schematic illustrations of a dividing cellbeing subjected to an electric field according to one exemplaryembodiment, resulting in destruction of the cell (FIG. 3C) in accordancewith one exemplary embodiment;

[0037]FIG. 4 is a schematic illustration of a dividing cell at one stagebeing subject to an electric field;

[0038]FIG. 5 is a schematic block diagram of an apparatus for applyingan electric according to one exemplary embodiment for selectivelydestroying cells;

[0039]FIG. 6 is a simplified schematic diagram of an equivalent electriccircuit of insulated electrodes of the apparatus of FIG. 5;

[0040]FIG. 7 is a cross-sectional illustration of a skin patchincorporating the apparatus of FIG. 5 and for placement on a skinsurface for treating a tumor or the like;

[0041]FIG. 8 is a cross-sectional illustration of the insulatedelectrodes implanted within the body for treating a tumor or the like;

[0042]FIG. 9 is a cross-sectional illustration of the insulatedelectrodes implanted within the body for treating a tumor or the like;

[0043] FIGS. 10A-10D are cross-sectional illustrations of variousconstructions of the insulated electrodes of the apparatus of FIG. 5;

[0044]FIG. 11 is a front elevational view in partial cross-section oftwo insulated electrodes being arranged about a human torso fortreatment of a tumor container within the body, e.g., a tumor associatedwith lung cancer;

[0045] FIGS. 12A-12C are cross-sectional illustrations of variousinsulated electrodes with and without protective members formed as apart of the construction thereof;

[0046]FIG. 13 is a schematic diagram of insulated electrodes that arearranged for focusing the electric field at a desired target whileleaving other areas in low field density (i.e., protected areas);

[0047]FIG. 14 is a cross-sectional view of insulated electrodesincorporated into a hat according to a first embodiment for placement ona head for treating an intra-cranial tumor or the like;

[0048]FIG. 15 is a partial section of a hat according to an exemplaryembodiment having a recessed section for receiving one or more insulatedelectrodes;

[0049]FIG. 16 is a cross-sectional view of the hat of FIG. 15 placed ona head and illustrating a biasing mechanism for applying a force to theinsulated electrode to ensure the insulated electrode remains in contactagainst the head;

[0050]FIG. 17 is a cross-sectional top view of an article of clothinghaving the insulated electrodes incorporated therein for treating atumor or the like;

[0051]FIG. 18 is a cross-sectional view of a section of the article ofclothing of FIG. 17 illustrating a biasing mechanism for biasing theinsulated electrode in direction to ensure the insulated electrode isplaced proximate to a skin surface where treatment is desired;

[0052]FIG. 19 is a cross-sectional view of a probe according to oneembodiment for being disposed internally within the body for treating atumor or the like;

[0053]FIG. 20 is an elevational view of an unwrapped collar according toone exemplary embodiment for placement around a neck for treating atumor or the like in this area when the collar is wrapped around theneck;

[0054]FIG. 21 is a cross-sectional view of two insulated electrodes withconductive gel members being arranged about a body, with the electricfield lines being shown;

[0055]FIG. 22 is a cross-sectional view of the arrangement of FIG. 21illustrating a point of insulation breakdown in one insulated electrode;

[0056]FIG. 23 is a cross-sectional view of an arrangement of at leasttwo insulated electrodes with conductive gel members being arrangedabout a body for treatment of a tumor or the like, wherein eachconductive gel member has a feature for minimizing the effects of aninsulation breakdown in the insulated electrode;

[0057]FIG. 24 is a cross-sectional view of another arrangement of atleast two insulated electrodes with conductive gel members beingarranged about a body for treatment of a tumor or the like, wherein aconductive member is disposed within the body near the tumor to create aregion of increased field density;

[0058]FIG. 25 is a cross-sectional view of an arrangement of twoinsulated electrodes of varying sizes disposed relative to a body; and

[0059]FIG. 26 is a cross-sectional view of an arrangement of at leasttwo insulated electrodes with conductive gel members being arrangedabout a body for treatment of a tumor or the like, wherein eachconductive gel member has a feature for minimizing the effects of aninsulation breakdown in the insulated electrode.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0060] Reference is made to FIGS. 1A-1E which schematically illustratevarious stages of a cell division process. FIG. 1A illustrates a cell 10at its normal geometry, which can be generally spherical (as illustratedin the drawings), ellipsoidal, cylindrical, “pancake-like” or any othercell geometry, as is known in the art. FIGS. 1B-1D illustrate cell 10during different stages of its division process, which results in theformation of two new cells 18 and 20, shown in FIG. 1E.

[0061] As shown in FIGS. 1B-1D, the division process of cell 10 ischaracterized by a slowly growing cleft 12 which gradually separatescell 10 into two units, namely sub-cells 14 and 16, which eventuallyevolve into new cells 18 and 20 (FIG. 1E). A shown specifically in FIG.1D, the division process is characterized by a transient period duringwhich the structure of cell 10 is basically that of the two sub-cells 14and 16 interconnected by a narrow “bridge” 22 containing cell material(cytoplasm surrounded by cell membrane).

[0062] Reference is now made to FIGS. 2A and 2B, which schematicallyillustrate non-dividing cell 10 being subjected to an electric fieldproduced by applying an alternating electric potential, at a relativelylow frequency and at a relatively high frequency, respectively. Cell 10includes intracellular organelles, e.g., a nucleus 30. Alternatingelectric potential is applied across electrodes 28 and 32 that can beattached externally to a patient at a predetermined region, e.g., in thevicinity of the tumor being treated. When cell 10 is under naturalconditions, i.e., part of a living tissue, it is disposed in aconductive environment (hereinafter referred to as a “volume conductor”)consisting mostly of electrolytic inter-cellular liquid. When anelectric potential is applied across electrodes 28 and 32, some of thefield lines of the resultant electric field (or the current induced inthe tissue in response to the electric field) penetrate the cell 10,while the rest of the field lines (or induced current) flow in thesurrounding medium. The specific distribution of the electric fieldlines, which is substantially consistent with the direction of currentflow in this instance, depends on the geometry and the electricproperties of the system components, e.g., the relative conductivitiesand dielectric constants of the system components, that can be frequencydependent. For low frequencies, e.g., frequencies lower than 10 KHz, theconductance properties of the components completely dominate the currentflow and the field distribution, and the field distribution is generallyas depicted in FIG. 2A. At higher frequencies, e.g., at frequencies ofbetween 10 KHz and 1 MHz, the dielectric properties of the componentsbecomes more significant and eventually dominate the field distribution,resulting in field distribution lines as depicted generally in FIG. 2B.

[0063] For constant (i.e., DC) electric fields or relatively lowfrequency alternating electric fields, for example, frequencies under 10KHz, the dielectric properties of the various components are notsignificant in determining and computing the field distribution.Therefore, as a first approximation, with regard to the electric fielddistribution, the system can be reasonably represented by the relativeimpedances of its various components. Using this approximation, theintercellular (i.e., extracellular) fluid and the intracellular fluideach has a relatively low impedance, while the cell membrane 11 has arelatively high impedance. Thus, under low frequency conditions, only afraction of the electric field lines (or currents induced by theelectric field) penetrate membrane 11 of the cell 10. At relatively highfrequencies (e.g., 10 KHz-1 MHz), in contrast, the impedance of membrane11 relative to the intercellular and intracellular fluids decreases, andthus, the fraction of currents penetrating the cells increasessignificantly. It should be noted that at very high frequencies, i.e.,above 1 MHz, the membrane capacitance can short the membrane resistanceand, therefore, the total membrane resistance can become negligible.

[0064] In any of the embodiments described above, the electric fieldlines (or induced currents) penetrate cell 10 from a portion of themembrane 11 closest to one of the electrodes generating the current,e.g., closest to positive electrode 28 (also referred to herein as“source”). The current flow pattern across cell 10 is generally uniformbecause, under the above approximation, the field induced inside thecell is substantially homogeneous. The currents exit cell 10 through aportion of membrane 11 closest to the opposite electrode, e.g., negativeelectrode 32 (also referred to herein as “sink”).

[0065] The distinction between field lines and current flow can dependon a number of factors, for example, on the frequency of the appliedelectric potential and on whether electrodes 28 and 32 are electricallyinsulated. For insulated electrodes applying a DC or low frequencyalternating voltage, there is practically no current flow along thelines of the electric field. At higher frequencies, the displacementcurrents are induced in the tissue due to charging and discharging ofthe electrode insulation and the cell membranes (which act as capacitorsto a certain extent), and such currents follow the lines of the electricfield. Fields generated by non-insulated electrodes, in contrast, alwaysgenerate some form of current flow, specifically, DC or low frequencyalternating fields generate conductive current flow along the fieldlines, and high frequency alternating fields generate both conductionand displacement currents along the field lines. It should beappreciated, however, that movement of polarizable intracellularorganelles according to the present invention (as described below) isnot dependent on actual flow of current and, therefore, both insulatedand non-insulated electrodes can be used efficiently. Several advantagesof insulated electrodes are that they have lower power consumption andcause less heating of the treated regions.

[0066] According to one exemplary embodiment of the present invention,the electric fields that are used are alternating fields havingfrequencies that are in the range from about 50 KHz to about 500 KHz,and preferably from about 100 KHz to about 300 KHz. For ease ofdiscussion, these type of electric fields are also referred to below as“TC fields”, which is an abbreviation of “Tumor Curing electric fields”,since these electric fields fall into an intermediate category (betweenhigh and low frequency ranges) that have bio-effective field propertieswhile having no meaningful stimulatory and thermal effects. Thesefrequencies are sufficiently low so that the system behavior isdetermined by the system's Ohmic (conductive) properties butsufficiently high enough not to have any stimulation effect on excitabletissues. Such a system consists of two types of elements, namely, theintercellular, or extracellular fluid, or medium and the individualcells. The intercellular fluid is mostly an electrolyte with a specificresistance of about 40-100 Ohm*cm. As mentioned above, the cells arecharacterized by three elements, namely (1) a thin, highly electricresistive membrane that coats the cell; (2) internal cytoplasm that ismostly an electrolyte that contains numerous macromolecules andmicro-organelles, including the nucleus; and (3) membranes, similar intheir electric properties to the cell membrane, cover themicro-organelles.

[0067] When this type of system is subjected to the present TC fields(e.g., alternating electric fields in the frequency range of 100 KHz-300KHz) most of the lines of the electric field and currents tend away fromthe cells because of the high resistive cell membrane and therefore thelines remain in the extracellular conductive medium. In the aboverecited frequency range, the actual fraction of electric field orcurrents that penetrates the cells is a strong function of thefrequency.

[0068]FIG. 2 schematically depicts the resulting field distribution inthe system. As illustrated, the lines of force, which also depict thelines of potential current flow across the cell volume mostly inparallel with the undistorted lines of force (the main direction of theelectric field). In other words, the field inside the cells is mostlyhomogeneous. In practice, the fraction of the field or current thatpenetrates the cells is determined by the cell membrane impedance valuerelative to that of the extracellular fluid. Since the equivalentelectric circuit of the cell membrane is that of a resistor andcapacitor in parallel, the impedance is a function of the frequency. Thehigher the frequency, the lower the impedance, the larger the fractionof penetrating current and the smaller the field distortion (RotshenkerS. & Y. Palti, Changes in fraction of current penetrating an axon as afunction of duration of stimulating pulse, J. Theor. Biol. 41; 401-407(1973).

[0069] As previously mentioned, when cells are subjected to relativelyweak electric fields and currents that alternate at high frequencies,such as the present TC fields having a frequency in the range of 50KHz-500 KHz, they have no effect on the non-dividing cells. While thepresent TC fields have no detectable effect on such systems, thesituation becomes different in the presence of dividing cells.

[0070] Reference is now made to FIGS. 3A-3C which schematicallyillustrate the electric current flow pattern in cell 10 during itsdivision process, under the influence of alternating fields (TC fields)in the frequency range from about 100 KHz to about 300 KHz in accordancewith one exemplary embodiment. The field lines or induced currentspenetrate cell 10 through a part of the membrane of sub-cell 16 closerto electrode 28. However, they do not exit through the cytoplasm bridge22 that connects sub-cell 16 with the newly formed yet still attachedsub-cell 14, or through a part of the membrane in the vicinity of thebridge 22. Instead, the electric field or current flow lines—that arerelatively widely separated in sub-cell 16—converge as they approachbridge 22 (also referred to as “neck” 22) and, thus, the current/fieldline density within neck 22 is increased dramatically. A “mirror image”process takes place in sub-cell 14, whereby the converging field linesin bridge 22 diverge as they approach the exit region of sub-cell 14.

[0071] It should be appreciated by persons skilled in the art thathomogeneous electric fields do not exert a force on electrically neutralobjects, i.e., objects having substantially zero net charge, althoughsuch objects can become polarized. However, under a non-uniform,converging electric field, as shown in FIGS. 3A-3C, electric forces areexerted on polarized objects, moving them in the direction of the higherdensity electric field lines. It will be appreciated that theconcentrated electric field that is present in the neck or bridge areain itself exerts strong forces on charges and natural dipoles and candisrupt structures that are associated therewith. One will understandthat similar net forces act on charges in an alternating field, again inthe direction of the field of higher intensity.

[0072] In the configuration of FIGS. 3A and 3B, the direction ofmovement of polarized and charged objects is towards the higher densityelectric field lines, i.e., towards the cytoplasm bridge 22 betweensub-cells 14 and 16. It is known in the art that all intracellularorganelles, for example, nuclei 24 and 26 of sub-cells 14 and 16,respectively, are polarizable and, thus, such intracellular organellesare electrically forced in the direction of the bridge 22. Since themovement is always from lower density currents to the higher densitycurrents, regardless of the field polarity, the forces applied by thealternating electric field to organelles, such as nuclei 24 and 26, arealways in the direction of bridge 22. A comprehensive description ofsuch forces and the resulting movement of macromolecules ofintracellular organelles, a phenomenon referred to as“dielectrophoresis” is described extensively in literature, e.g., in C.L. Asbury & G. van den Engh, Biophys. J. 74, 1024-1030, 1998, thedisclosure of which is hereby incorporated by reference in its entirety.

[0073] The movement of the organelles 24 and 26 towards the bridge 22disrupts the structure of the dividing cell, change the concentration ofthe various cell constituents and, eventually, the pressure of theconverging organelles on bridge membrane 22 results in the breakage ofcell membrane 11 at the vicinity of the bridge 22, as shownschematically in FIG. 3C. The ability to break membrane 11 at bridge 22and to otherwise disrupt the cell structure and organization can beenhanced by applying a pulsating AC electric field, rather than a steadyAC field. When a pulsating field is applied, the forces acting onorganelles 24 and 26 have a “hammering” effect, whereby pulsed forcesbeat on the intracellular organelles towards the neck 22 from bothsub-cells 14 and 16, thereby increasing the probability of breaking cellmembrane 11 in the vicinity of neck 22.

[0074] A very important element, which is very susceptible to thespecial fields that develop within the dividing cells is the microtubulespindle that plays a major role in the division process. In FIG. 4, adividing cell 10 is illustrated, at an earlier stage as compared toFIGS. 3A and 3B, under the influence of external TC fields (e.g.,alternating fields in the frequency range of about 100 KHz to about 300KHz), generally indicated as lines 100, with a corresponding spindlemechanism generally indicated at 120. The lines 120 are microtubulesthat are known to have a very strong dipole moment. This strongpolarization makes the tubules, as well as other polar macromoleculesand especially those that have a specific orientation within the cellsor its surrounding, susceptible to electric fields. Their positivecharges are located at the two centrioles while two sets of negativepoles are at the center of the dividing cell and the other pair is atthe points of attachment of the microtubules to the cell membrane,generally indicated at 130. This structure forms sets of double dipolesand therefore they are susceptible to fields of different directions. Itwill be understood that the effect of the TC fields on the dipoles doesnot depend on the formation of the bridge (neck) and thus, the dipolesare influenced by the TC fields prior to the formation of the bridge(neck).

[0075] Since the present apparatus (as will be described in greaterdetail below) utilizes insulated electrodes, the above-mentionednegative effects obtained when conductive electrodes are used, i.e., ionconcentration changes in the cells and the formation of harmful agentsby electrolysis, do not occur when the present apparatus is used. Thisis because, in general, no actual transfer of charges takes placebetween the electrodes and the medium and there is no charge flow in themedium where the currents are capacitive, i.e., are expressed only asrotation of charges, etc.

[0076] Turning now to FIG. 5, the TC fields described above that havebeen found to advantageously destroy tumor cells are generated by anelectronic apparatus 200. FIG. 5 is a simple schematic diagram of theelectronic apparatus 200 illustrating the major components thereof. Theelectronic apparatus 200 generates the desired electric signals (TCsignals) in the shape of waveforms or trains of pulses. The apparatus200 includes a generator 210 and a pair of conductive leads 220 that areattached at one end thereof to the generator 210. The opposite ends ofthe leads 220 are connected to insulated conductors 230 that areactivated by the electric signals (e.g., waveforms). The insulatedconductors 230 are also referred to hereinafter as isolects 230.Optionally and according to another exemplary embodiment, the apparatus200 includes a temperature sensor 240 and a control box 250 which areboth added to control the amplitude of the electric field generated soas not to generate excessive heating in the area that is treated.

[0077] The generator 210 generates an alternating voltage waveform atfrequencies in the range from about 50 KHz to about 500 KHz (preferablyfrom about 100 KHz to about 300 KHz) (i.e., the TC fields). The requiredvoltages are such that the electric field intensity in the tissue to betreated is in the range of about 0.1 V/cm to about 10 V/cm. To achievethis field, the actual potential difference between the two conductorsin the isolects 230 is determined by the relative impedances of thesystem components, as described below.

[0078] When the control box 250 is included, it controls the output ofthe generator 210 so that it will remain constant at the value preset bythe user or the control box 250 sets the output at the maximal valuethat does not cause excessive heating, or the control box 250 issues awarning or the like when the temperature (sensed by temperature sensor240) exceeds a preset limit.

[0079] The leads 220 are standard isolated conductors with a flexiblemetal shield, preferably grounded so that it prevents the spread of theelectric field generated by the leads 220. The isolects 230 havespecific shapes and positioning so as to generate an electric field ofthe desired configuration, direction and intensity at the target volumeand only there so as to focus the treatment.

[0080] The specifications of the apparatus 200 as a whole and itsindividual components are largely influenced by the fact that at thefrequency of the present TC fields (50 KHz-500 KHz), living systemsbehave according to their “Ohmic”, rather than their dielectricproperties. The only elements in the apparatus 200 that behavedifferently are the insulators of the isolects 230 (see FIGS. 7-9). Theisolects 200 consist of a conductor in contact with a dielectric that isin contact with the conductive tissue thus forming a capacitor.

[0081] The details of the construction of the isolects 230 is based ontheir electric behavior that can be understood from their simplifiedelectric circuit when in contact with tissue as generally illustrated inFIG. 6. In the illustrated arrangement, the potential drop or theelectric field distribution between the different components isdetermined by their relative electric impedance, i.e., the fraction ofthe field on each component is given by the value of its impedancedivided by the total circuit impedance. For example, the potential dropon element Δ V_(A)=A/(A+B+C+D+E). Thus, for DC or low frequency AC,practically all the potential drop is on the capacitor (that acts as aninsulator). For relatively very high frequencies, the capacitorpractically is a short and therefore, practically all the field isdistributed in the tissues. At the frequencies of the present TC fields(e.g., 50 KHz to 500 KHz), which are intermediate frequencies, theimpedance of the capacitance of the capacitors is dominant anddetermines the field distribution. Therefore, in order to increase theeffective voltage drop across the tissues (field intensity), theimpedance of the capacitors is to be decreased (i.e., increase theircapacitance). This can be achieved by increasing the effective area ofthe “plates” of the capacitor, decrease the thickness of the dielectricor use a dielectric with high dielectric constant.

[0082] In order to optimize the field distribution, the isolects 230 areconfigured differently depending upon the application in which theisolects 230 are to be used. There are two principle modes for applyingthe present electric fields (TC fields). First, the TC fields can beapplied by external isolects and second, the TC fields can be applied byinternal isolects.

[0083] Electric fields (TC fields) that are applied by external isolectscan be of a local type or widely distributed type. The first typeincludes, for example, the treatment of skin tumors and treatment oflesions close to the skin surface. FIG. 7 illustrates an exemplaryembodiment where the isolects 230 are incorporated in a skin patch 300.The skin patch 300 can be a self-adhesive flexible patch with one ormore pairs of isolects 230. The patch 300 includes internal insulation310 (formed of a dielectric material) and the external insulation 260and is applied to skin surface 301 that contains a tumor 303 either onthe skin surface 301 or slightly below the skin surface 301. Tissue isgenerally indicated at 305. To prevent the potential drop across theinternal insulation 310 to dominate the system, the internal insulation310 must have a relatively high capacity. This can be achieved by alarge surface area; however, this may not be desired as it will resultin the spread of the field over a large area (e.g., an area larger thanrequired to treat the tumor). Alternatively, the internal insulation 310can be made very thin and/or the internal insulation 310 can be of ahigh dielectric constant. As the skin resistance between the electrodes(labeled as A and E in FIG. 6) is normally significantly higher thanthat of the tissue (labeled as C in FIG. 6) underneath it (1-10 KΩ vs.0.1-1 KΩ), most of the potential drop beyond the isolects occurs there.To accommodate for these impedances (Z), the characteristics of theinternal insulation 310 (labeled as B and D in FIG. 6) should be suchthat they have impedance preferably under 100 KΩ at the frequencies ofthe present TC fields (e.g., 50 KHz to 500 KHz). For example, if it isdesired for the impedance to be about 10 K Ohms or less, such that over1% of the applied voltage falls on the tissues, for isolects with asurface area of 10 mm², at frequencies of 200 KHz, the capacity shouldbe on the order of 10⁻¹⁰ F., which means that using standard insulationswith a dielectric constant of 2-3, the thickness of the insulating layer310 should be about 50-100 microns. An internal field 10 times strongerwould be obtained with insulators with a dielectric constant of about20-50.

[0084] Since the thin insulating layer can be very vulnerable, etc., theinsulation can be replaced by very high dielectric constant insulatingmaterials, such as titanium dioxide (e.g., rutil), the dielectricconstant can reach values of about 200. There a number of differentmaterials that are suitable for use in the intended application and havehigh dielectric constants. For example, some materials include: lithiumnibate (LiNbO₃), which is a ferroelectric crystal and has a number ofapplications in optical, pyroelectric and piezoelectric devices;yittrium iron garnet (YIG) is a ferrimagnetic crystal andmagneto-optical devices, e.g., optical isolator can be realized fromthis material; barium titanate (BaTiO₃) is a ferromagnetic crystal witha large electro-optic effect; potassium tantalate (KTaO₃) which is adielectric crystal (ferroelectric at low temperature) and has very lowmicrowave loss and tunability of dielectric constant at low temperature;and lithium tantalate (LiTaO₃) which is a ferroelectric crystal withsimilar properties as lithium niobate and has utility inelectro-optical, pyroelectric and piezoelectric devices. It will beunderstood that the aforementioned exemplary materials can be used incombination with the present device where it is desired to use amaterial having a high dielectric constant.

[0085] One must also consider another factor that effects the effectivecapacity of the isolects 230, namely the presence of air between theisolects 230 and the skin. Such presence, which is not easy to prevent,introduces a layer of an insulator with a dielectric constant of 1.0, afactor that significantly lowers the effective capacity of the isolects230 and neutralizes the advantages of the titanium dioxide (routil),etc. To overcome this problem, the isolects 230 can be shaped so as toconform with the body structure and/or (2) an intervening filler 270 (asillustrated in FIG. 10C), such as a gel, that has high conductance and ahigh effective dielectric constant, can be added to the structure. Theshaping can be pre-structured (see FIG. 10A) or the system can be madesufficiently flexible so that shaping of the isolects 230 is readilyachievable. The gel can be contained in place by having an elevated rimas depicted in FIGS. 10C and 10C′. The gel can be made of hydrogels,gelatins, agar, etc., and can have salts dissolved in it to increase itsconductivity. FIGS. 10A-10C′ illustrate various exemplary configurationsfor the isolects 230. The exact thickness of the gel is not important solong as it is of sufficient thickness that the gel layer does not dryout during the treatment. In one exemplary embodiment, the thickness ofthe gel is about 0.5 mm to about 2 mm.

[0086] In order to achieve the desirable features of the isolects 230,the dielectric coating of each should be very thin, for example frombetween 1-50 microns. Since the coating is so thin, the isolects 230 caneasily be damaged mechanically. This problem can be overcome by adding aprotective feature to the isolect's structure so as to provide desiredprotection from such damage. For example, the isolect 230 can be coated,for example, with a relatively loose net 340 that prevents access to thesurface but has only a minor effect on the effective surface area of theisolect 230 (i.e., the capacity of the isolects 230 (cross sectionpresented in FIG. 12B). The loose net 340 does not effect the capacityand ensures good contact with the skin, etc. The loose net 340 can beformed of a number of different materials; however, in one exemplaryembodiment, the net 340 is formed of nylon, polyester, cotton, etc.Alternatively, a very thin conductive coating 350 can be applied to thedielectric portion (insulating layer) of the isolect 230. One exemplaryconductive coating is formed of a metal and more particularly of gold.The thickness of the coating 350 depends upon the particular applicationand also on the type of material used to form the coating 350; however,when gold is used, the coating has a thickness from about 0.1 micron toabout 0.1 mm. Furthermore, the rim illustrated in FIG. 10 can alsoprovide some mechanical protection.

[0087] However, the capacity is not the only factor to be considered.The following two factors also influence how the isolects 230 areconstructed. The dielectric strength of the internal insulating layer310 and the dielectric losses that occur when it is subjected to the TCfield, i.e., the amount of heat generated. The dielectric strength ofthe internal insulation 310 determines at what field intensity theinsulation will be “shorted” and cease to act as an intact insulation.Typically, insulators, such as plastics, have dielectric strength valuesof about 100V per micron or more. As a high dielectric constant reducesthe field within the internal insulator 310, a combination of a highdielectric constant and a high dielectric strength gives a significantadvantage. This can be achieved by using a single material that has thedesired properties or it can be achieved by a double layer with thecorrect parameters and thickness. In addition, to further decreasing thepossibility that the insulating layer 310 will fail, all sharp edges ofthe insulating layer 310 should be eliminated as by rounding thecorners, etc., as illustrated in FIG. 10D using conventional techniques.

[0088]FIGS. 8 and 9 illustrate a second type of treatment using theisolects 230, namely electric field generation by internal isolects 230.A body to which the isolects 230 are implanted is generally indicated at311 and includes a skin surface 313 and a tumor 315. In this embodiment,the isolects 230 can have the shape of plates, wires or other shapesthat can be inserted subcutaneously or a deeper location within the body311 so as to generate an appropriate field at the target area (tumor315).

[0089] It will also be appreciated that the mode of isolects applicationis not restricted to the above descriptions. In the case of tumors ininternal organs, for example, liver, lung, etc., the distance betweeneach member of the pair of isolects 230 can be large. The pairs can evenby positioned opposite sides of a torso 410, as illustrated in FIG. 11.The arrangement of the isolects 230 in FIG. 11 is particularly usefulfor treating a tumor 415 associated with lung cancer orgastro-intestinal tumors. In this embodiment, the electric fields (TCfields) spread in a wide fraction of the body.

[0090] In order to avoid overheating of the treated tissues, a selectionof materials and field parameters is needed. The isolects insulatingmaterial should have minimal dielectric losses at the frequency rangesto be used during the treatment process. This factor can be taken intoconsideration when choosing the particular frequencies for thetreatment. The direct heating of the tissues will most likely bedominated by the heating due to current flow (given by the I*R product).In addition, the isolect (insulated electrode) 230 and its surroundingsshould be made of materials that facilitate heat losses and its generalstructure should also facilitate head losses, i.e., minimal structuresthat block heat dissipation to the surroundings (air) as well as highheat conductivity.

[0091] The effectiveness of the treatment can be enhanced by anarrangement of isolects 230 that focuses the field at the desired targetwhile leaving other sensitive areas in low field density (i.e.,protected areas). The proper placement of the isolects 230 over the bodycan be maintained using any number of different techniques, includingusing a suitable piece of clothing that keeps the isolects at theappropriate positions. FIG. 13 illustrates such an arrangement in whichan area labeled as “P” represents a protected area. The lines of fieldforce do not penetrate this protected area and the field there is muchsmaller than near the isolects 230 where target areas can be located andtreated well. In contrast, the field intensity near the four poles isvery high.

[0092] The following Example serves to illustrate an exemplaryapplication of the present apparatus and application of TC fields;however, this Example is not limiting and does not limit the scope ofthe present invention in any way.

EXAMPLE

[0093] To demonstrate the effectiveness of electric fields having theabove described properties (e.g., frequencies between 50 KHz and 500KHz) in destroying tumor cells, the electric fields were applied totreat mice with malignant melanoma tumors. Two pairs of isolects 230were positioned over a corresponding pair of malignant melanomas. Onlyone pair was connected to the generator 210 and 200 KHz alternatingelectric fields (TC fields) were applied to the tumor for a period of 6days. One melanoma tumor was not treated so as to permit a comparisonbetween the treated tumor and the non-treated tumor. After treatment for6 days, the pigmented melanoma tumor remained clearly visible in thenon-treated side of the mouse, while, in contrast, no tumor is seen onthe treated side of the mouse. The only areas that were visiblediscernable on the skin were the marks that represented the points ofinsertion of the isolects 230. The fact that the tumor was eliminated atthe treated side was further demonstrated by cutting and inversing theskin so that its inside face was exposed. Such a procedure indicatedthat the tumor has been substantially, if not completely, eliminated onthe treated side of the mouse. The success of the treatment was alsofurther verified by pathhistological examination.

[0094] The present inventor has thus uncovered that electric fieldshaving particular properties can be used to destroy dividing cells ortumors when the electric fields are applied to using an electronicdevice. More specifically, these electric fields fall into a specialintermediate category, namely bio-effective fields that have nomeaningful stimulatory and no thermal effects, and therefore overcomethe disadvantages that were associated with the application ofconventional electric fields to a body. It will also be appreciated thatthe present apparatus can further include a device for rotating the TCfield relative to the living tissue. For example and according to oneembodiment, the alternating electric potential applies to the tissuebeing treated is rotated relative to the tissue using conventionaldevices, such as a mechanical device that upon activation, rotatesvarious components of the present system.

[0095] Moreover and according to yet another embodiment, the TC fieldsare applied to different pairs of the insulated electrodes 230 in aconsecutive manner. In other words, the generator 210 and the controlsystem thereof can be arranged so that signals are sent at periodicintervals to select pairs of insulated electrodes 230, thereby causingthe generation of the TC fields of different directions by theseinsulated electrodes 230. Because the signals are sent at select timesfrom the generator to the insulated electrodes 230, the TC fields ofchanging directions are generated consecutively by different insulatedelectrodes 230. This arrangement has a number of advantages and isprovided in view of the fact that the TC fields have maximal effect whenthey are parallel to the axis of cell division. Since the orientation ofcell division is in most cases random, only a fraction of the dividingcells are affected by any given field. Thus, using fields of two or moreorientations increases the effectiveness since it increases the chancesthat more dividing cells are affected by a given TC field.

[0096] Turning now to FIG. 14 in which an article of clothing 500according to one exemplary embodiment is illustrated. More specifically,the article of clothing 500 is in the form of a hat or cap or other typeof clothing designed for placement on a head of a person. For purposesof illustration, a head 502 is shown with the hat 500 being placedthereon and against a skin surface 504 of the head 502. An intra-cranialtumor or the like 510 is shown as being formed within the head 502underneath the skin surface 504 thereof. The hat 500 is thereforeintended for placement on the head 502 of a person who has a tumor 510or the like.

[0097] Unlike the various embodiments illustrated in FIGS. 1-13 wherethe insulated electrodes 230 are arranged in a more or less planararrangement since they are placed either on a skin surface or embeddedwithin the body underneath it, the insulated electrodes 230 in thisembodiment are specifically contoured and arranged for a specificapplication. The treatment of intra-cranial tumors or other lesions orthe like typically requires a treatment that is of a relatively longduration, e.g., days to weeks, and therefore, it is desirable to provideas much comfort as possible to the patient. The hat 500 is specificallydesigned to provide comfort during the lengthy treatment process whilenot jeopardizing the effectiveness of the treatment.

[0098] According to one exemplary embodiment, the hat 500 includes apredetermined number of insulated electrodes 230 that are preferablypositioned so as to produce the optimal TC fields at the location of thetumor 510. The lines of force of the TC field are generally indicated at520. As can be seen in FIG. 14, the tumor 510 is positioned within theselines of force 520. As will be described in greater detail hereinafter,the insulated electrodes 230 are positioned within the hat 500 such thata portion or surface thereof is free to contact the skin surface 504 ofthe head 502. In other words, when the patient wears the hat 500, theinsulated electrodes 230 are placed in contact with the skin surface 504of the head 502 in positions that are selected so that the TC fieldsgenerated thereby are focused at the tumor 510 while leaving surroundingareas in low density. Typically, hair on the head 502 is shaved inselected areas to permit better contact between the insulated electrodes230 and the skin surface 504; however, this is not critical.

[0099] The hat 500 preferably includes a mechanism 530 that applies orforce to the insulated electrodes 230 so that they are pressed againstthe skin surface 502. For example, the mechanism 530 can be of a biasingtype that applies a biasing force to the insulated electrodes 230 tocause the insulated electrodes 230 to be directed outwardly away fromthe hat 500. Thus, when the patient places the hat 500 on his/her head502, the insulated electrodes 230 are pressed against the skin surface504 by the mechanism 530. The mechanism 530 can slightly recoil toprovide a comfortable fit between the insulated electrodes 230 and thehead 502. In one exemplary embodiment, the mechanism 530 is a springbased device that is disposed within the hat 500 and has one sectionthat is coupled to and applies a force against the insulated electrodes230.

[0100] As with the prior embodiments, the insulated electrodes 230 arecoupled to the generator 210 by means of conductors 220. The generator210 can be either disposed within the hat 500 itself so as to provide acompact, self-sufficient, independent system or the generator 210 can bedisposed external to the hat 500 with the conductors 220 exiting the hat500 through openings or the like and then running to the generator 210.When the generator 210 is disposed external to the hat 500, it will beappreciated that the generator 210 can be located in any number ofdifferent locations, some of which are in close proximity to the hat 500itself, while others can be further away from the hat 500. For example,the generator 210 can be disposed within a carrying bag or the like(e.g., a bag that extends around the patient's waist) which is worn bythe patient or it can be strapped to an extremity or around the torso ofthe patient. The generator 210 can also be disposed in a protective casethat is secured to or carried by another article of clothing that isworn by the patient. For example, the protective case can be insertedinto a pocket of a sweater, etc. FIG. 14 illustrates an embodiment wherethe generator 210 is incorporated directly into the hat 500.

[0101] Turning now to FIGS. 15 and 16, in one exemplary embodiment, anumber of insulated electrodes 230 along with the mechanism 530 arepreferably formed as an independent unit, generally indicated at 540,that can be inserted into the hat 500 and electrically connected to thegenerator (not shown) via the conductors (not shown). By providing thesemembers in the form of an independent unit, the patient can easilyinsert and/or remove the units 540 from the hat 500 when they may needcleaning, servicing and/or replacement.

[0102] In this embodiment, the hat 500 is constructed to include selectareas 550 that are formed in the hat 500 to receive and hold the units540. For example and as illustrated in FIG. 15, each area 550 is in theform of an opening (pore) that is formed within the hat 500. The unit540 has a body 542 and includes the mechanism 530 and one or moreinsulated electrodes 230. The mechanism 530 is arranged within the unit540 so that a portion thereof (e.g., one end thereof) is in contact witha face of each insulated electrode 230 such that the mechanism 530applies a biasing force against the face of the insulated electrode 230.Once the unit 540 is received within the opening 550, it can be securelyretained therein using any number of conventional techniques, includingthe use of an adhesive material or by using mechanical means. Forexample, the hat 500 can include pivotable clip members that pivotbetween an open position in which the opening 550 is free and a closedposition in which the pivotable clip members engage portions (e.g.,peripheral edges) of the insulated electrodes to retain and hold theinsulated electrodes 230 in place. To remove the insulated electrodes230, the pivotable clip members are moved to the open position. In theembodiment illustrated in FIG. 16, the insulated electrodes 230 areretained within the openings 550 by an adhesive element 560 which in oneembodiment is a two sided self-adhesive rim member that extends aroundthe periphery of the insulated electrode 230. In other words, aprotective cover of one side of the adhesive rim 560 is removed and itis applied around the periphery of the exposed face of the insulatedelectrode 230, thereby securely attaching the adhesive rim 560 to thehat 500 and then the other side of the adhesive rim 560 is removed forapplication to the skin surface 504 in desired locations for positioningand securing the insulated electrode 230 to the head 502 with the tumorbeing positioned relative thereto for optimization of the TC fields.Since one side of the adhesive rim 560 is in contact with and secured tothe skin surface 540, this is why it is desirable for the head 502 to beshaved so that the adhesive rim 560 can be placed flushly against theskin surface 540.

[0103] The adhesive rim 560 is designed to securely attach the unit 540within the opening 550 in a manner that permits the unit 540 to beeasily removed from the hat 500 when necessary and then replaced withanother unit 540 or with the same unit 540. As previously mentioned, theunit 540 includes the biasing mechanism 530 for pressing the insulatedelectrode 230 against the skin surface 504 when the hat 500 is worn. Theunit 540 can be constructed so that side opposite the insulatedelectrode 230 is a support surface formed of a rigid material, such asplastic, so that the biasing mechanism 530 (e.g., a spring) can becompressed therewith under the application of force and when the spring530 is in a relaxed state, the spring 530 remains in contact with thesupport surface and the applies a biasing force at its other end againstthe insulated electrode 230. The biasing mechanism 530 (e.g., spring)preferably has a contour corresponding to the skin surface 504 so thatthe insulated electrode 230 has a force applied thereto to permit theinsulated electrode 230 to have a contour complementary to the skinsurface 504, thereby permitting the two to seat flushly against oneanother. While the mechanism 530 can be a spring, there are a number ofother embodiments that can be used instead of a spring. For example, themechanism 530 can be in the form of an elastic material, such as a foamrubber, a foam plastic, or a layer containing air bubbles, etc.

[0104] The unit 540 has an electric connector 570 that can be hooked upto a corresponding electric connector, such as a conductor 220, that isdisposed within the hat 500. The conductor 220 connects at one end tothe unit 540 and at the other end is connected to the generator 210. Thegenerator 210 can be incorporated directly into the hat 500 or thegenerator 210 can be positioned separately (remotely) on the patient oron a bedside support, etc.

[0105] As previously discussed, a coupling agent, such as a conductivegel, is preferably used to ensure that an effective conductiveenvironment is provided between the insulated electrode 230 and the skinsurface 504. Suitable gel materials have been disclosed hereinbefore inthe discussion of earlier embodiments. The coupling agent is disposed onthe insulated electrode 230 and preferably, a uniform layer of the agentis provided along the surface of the electrode 230. One of the reasonsthat the units 540 need replacement at periodic times is that thecoupling agent needs to be replaced and/or replenished. In other words,after a predetermined time period or after a number of uses, the patientremoves the units 540 so that the coupling agent can be applied again tothe electrode 230.

[0106]FIGS. 17 and 18 illustrate another article of clothing which hasthe insulated electrodes 230 incorporated as part thereof. Morespecifically, a bra or the like 700 is illustrated and includes a bodythat is formed of a traditional bra material, generally indicated at705, to provide shape, support and comfort to the wearer. The bra 700also includes a fabric support layer 710 on one side thereof. Thesupport layer 710 is preferably formed of a suitable fabric materialthat is constructed to provide necessary and desired support to the bra700.

[0107] Similar to the other embodiments, the bra 700 includes one ormore insulated electrodes 230 disposed within the bra material 705. Theone or more insulated electrodes are disposed along an inner surface ofthe bra 700 opposite the support 710 and are intended to be placedproximate to a tumor or the like that is located within one breast or inthe immediately surrounding area. As with the previous embodiment, theinsulated electrodes 230 in this embodiment are specifically constructedand configured for application to a breast or the immediate area. Thus,the insulated electrodes 230 used in this application do not have aplanar surface construction but rather have an arcuate shape that iscomplementary to the general curvature found in a typical breast.

[0108] A lining 720 is disposed across the insulated electrodes 230 soas to assist in retaining the insulated electrodes in their desiredlocations along the inner surface for placement against the breastitself. The lining 720 can be formed of any number of thin materialsthat are comfortable to wear against one's skin and in one exemplaryembodiment, the lining 720 is formed of a fabric material.

[0109] The bra 700 also preferably includes a biasing mechanism 800 asin some of the earlier embodiments. The biasing mechanism 800 isdisposed within the bra material 705 and extends from the support 710 tothe insulated electrode 230 and applies a biasing force to the insulatedelectrode 230 so that the electrode 230 is pressed against the breast.This ensures that the insulated electrode 230 remains in contact withthe skin surface as opposed to lifting away from the skin surface,thereby creating a gap that results in a less effective treatment sincethe gap diminishes the efficiency of the TC fields. The biasingmechanism 800 can be in the form of a spring arrangement or it can be anelastic material that applies the desired biasing force to the insulatedelectrodes 230 so as to press the insulated electrodes 230 into thebreast. In the relaxed position, the biasing mechanism 800 applies aforce against the insulated electrodes 230 and when the patient placesthe bra 700 on their body, the insulated electrodes 230 are placedagainst the breast which itself applies a force that counters thebiasing force, thereby resulting in the insulated electrodes 230 beingpressed against the patient's breast. In the exemplary embodiment thatis illustrated, the biasing mechanism 800 is in the form of springs thatare disposed within the bra material 705.

[0110] A conductive gel 810 can be provided on the insulated electrode230 between the electrode and the lining 720. The conductive gel layer810 is formed of materials that have been previously described hereinfor performing the functions described above.

[0111] An electric connector 820 is provided as part of the insulatedelectrode 230 and electrically connects to the conductor 220 at one endthereof, with the other end of the conductor 220 being electricallyconnected to the generator 210. In this embodiment, the conductor 220runs within the bra material 705 to a location where an opening isformed in the bra 700. The conductor 220 extends through this openingand is routed to the generator 210, which in this embodiment is disposedin a location remote from the bra 700. It will also be appreciated thatthe generator 210 can be disposed within the bra 700 itself in anotherembodiment. For example, the bra 700 can have a compartment formedtherein which is configured to receive and hold the generator 210 inplace as the patient wears the bra 700. In this arrangement, thecompartment can be covered with a releasable strap that can open andclose to permit the generator 210 to be inserted therein or removedtherefrom. The strap can be formed of the same material that is used toconstruct the bra 700 or it can be formed of some other type ofmaterial. The strap can be releasably attached to the surrounding brabody by fastening means, such as a hook and loop material, therebypermitting the patient to easily open the compartment by separating thehook and loop elements to gain access to the compartment for eitherinserting or removing the generator 210.

[0112] The generator 210 also has a connector 211 for electricalconnection to the conductor 220 and this permits the generator 210 to beelectrically connected to the insulated electrodes 230.

[0113] As with the other embodiments, the insulated electrodes 230 arearranged in the bra 700 to focus the electric field (TC fields) on thedesired target (e.g., a tumor). It will be appreciated that the locationof the insulated electrodes 230 within the bra 700 will vary dependingupon the location of the tumor. In other words, after the tumor has beenlocated, the physician will then devise an arrangement of insulatedelectrodes 230 and the bra 700 is constructed in view of thisarrangement so as to optimize the effects of the TC fields on the targetarea (tumor). The number and position of the insulated electrodes 230will therefore depend upon the precise location of the tumor or othertarget area that is being treated. Because the location of the insulatedelectrodes 230 on the bra 700 can vary depending upon the preciseapplication, the exact size and shape of the insulated electrodes 230can likewise vary. For example, if the insulated electrodes 230 areplaced on the bottom section of the bra 700 as opposed to a more centrallocation, the insulated electrodes 230 will have different shapes sincethe shape of the breast (as well as the bra) differs in these areas.

[0114]FIG. 19 illustrates yet another embodiment in which the insulatedelectrodes 230 are in the form of internal electrodes that areincorporated into in the form of a probe or catheter 600 that isconfigured to enter the body through a natural pathway, such as theurethra, vagina, etc. In this embodiment, the insulated electrodes 230are disposed on an outer surface of the probe 600 and along a lengththereof. The conductors 220 are electrically connected to the electrodes230 and run within the body of the probe 600 to the generator 210 whichcan be disposed within the probe body or the generator 210 can bedisposed independent of the probe 600 in a remote location, such as onthe patient or at some other location close to the patient.

[0115] Alternatively, the probe 600 can be configured to penetrate theskin surface or other tissue to reach an internal target that lieswithin the body. For example, the probe 600 can penetrate the skinsurface and then be positioned adjacent to or proximate to a tumor thatis located within the body.

[0116] In these embodiments, the probe 600 is inserted through thenatural pathway and then is positioned in a desired location so that theinsulated electrodes 230 are disposed near the target area (i.e., thetumor). The generator 210 is then activated to cause the insulatedelectrodes 230 to generate the TC fields which are applied to the tumorfor a predetermined length of time. It will be appreciated that theillustrated probe 600 is merely exemplary in nature and that the probe600 can have other shapes and configurations so long as they can performthe intended function. Preferably, the conductors (e.g., wires) leadingfrom the insulated electrodes 230 to the generator 210 are twisted orshielded so as not to generate a field along the shaft.

[0117] It will further be appreciated that the probes can contain onlyone insulated electrode while the other can be positioned on the bodysurface. This external electrode should be larger or consist of numerouselectrodes so as to result in low lines of force-current density so asnot to affect the untreated areas. In fact, the placing of electrodesshould be designed to minimize the field at potentially sensitive areas.

[0118]FIG. 20 illustrates yet another embodiment in which a highstanding collar member 900 (or necklace type structure) can be used totreat thyroid, parathyroid, laryngeal lesions, etc. FIG. 20 illustratesthe collar member 900 in an unwrapped, substantially flat condition. Inthis embodiment, the insulated electrodes 230 are incorporated into abody 910 of the collar member 900 and are configured for placementagainst a neck area of the wearer. The insulated electrodes 230 arecoupled to the generator 210 according to any of the manner describedhereinbefore and it will be appreciated that the generator 210 can bedisposed within the body 910 or it can be disposed in a locationexternal to the body 910. The collar body 910 can be formed of anynumber of materials that are traditionally used to form collars 900 thatare disposed around a person's neck. As such, the collar 900 preferablyincludes a means 920 for adjusting the collar 900 relative to the neck.For example, complementary fasteners (hook and loop fasteners, buttons,etc.) can be disposed on ends of the collar 900 to permit adjustment ofthe collar diameter.

[0119] Thus, the construction of the present devices are particularlywell suited for applications where the devices are incorporated intoarticles of clothing to permit the patient to easily wear a traditionalarticle of clothing while at the same time the patient undergoestreatment. In other words, an extra level of comfort can be provided tothe patient and the effectiveness of the treatment can be increased byincorporating some or all of the device components into the article ofclothing. The precise article of clothing that the components areincorporated into will obviously vary depending upon the target area ofthe living tissue where tumor, lesion or the like exists. For example,if the target area is in the testicle area of a male patient, then anarticle of clothing in the form of a sock-like structure or wrap can beprovided and is configured to be worn around the testicle area of thepatient in such a manner that the insulated electrodes thereof arepositioned relative to the tumor such that the TC fields are directed atthe target tissue. The precise nature or form of the article of clothingcan vary greatly since the device components can be incorporated intomost types of articles of clothing and therefore, can be used to treatany number of different areas of the patient's body where a conditionmay be present.

[0120] Now turning to FIGS. 21-22 in which another aspect of the presentdevice is shown. In FIG. 21, a body 1000, such as any number of parts ofa human or animal body, is illustrated. As in the previous embodiments,two or more insulated electrodes 230 are disposed in proximity to thebody 1000 for treatment of a tumor or the like (not shown) using TCfields, as has been previously described in great detail in the abovediscussion of other embodiments. The insulated electrode 230 has aconductive component and has external insulation 260 that surrounds theconductive component thereof. Each insulated electrode 230 is preferablyconnected to a generator (not shown) by the lead 220. Between eachinsulated electrode 220 and the body 1000, a conductive filler material(e.g., conductive gel member 270) is disposed. The insulated electrodes230 are spaced apart from one another and when the generator isactuated, the insulated electrodes 230 generate the TC fields that havebeen previously described in great detail. The lines of the electricfield (TC field) are generally illustrated at 1010. As shown, theelectric field lines 1010 extend between the insulated electrodes 230and through the conductive gel member 270.

[0121] Over time or as a result of some type of event, the externalinsulation 260 of the insulated electrode 230 can begin to breakdown atany given location thereof. For purpose of illustration only, FIG. 22illustrates that the external insulation 260 of one of the insulatedelectrodes 230 has experienced a breakdown 1020 at a face thereof whichis adjacent the conductive gel member 270. It will be appreciated thatthe breakdown 1020 of the external insulation 260 results in theformation of a strong current flow-current density at this point (i.e.,at the breakdown 1020). The increased current density is depicted by theincreased number of electric field lines 1010 and the relativepositioning and distance between adjacent electric field lines 1010. Oneof the side effects of the occurrence of breakdown 1020 is that currentexists at this point which will generate heat and may burn thetissues/skin which have a resistance. In FIG. 22, an overheated area1030 is illustrated and is a region or area of the tissues/skin where anincreased current density exits due to the breakdown 1020 in theexternal insulation 260. A patient can experience discomfort and pain inthis area 1030 due to the strong current that exists in the area and theincreased heat and possible burning sensation that exist in area 1030.

[0122]FIG. 23 illustrates yet another embodiment in which a furtherapplication of the insulated electrodes 230 is shown. In thisembodiment, the conductive gel member 270 that is disposed between theinsulated electrode 230 and the body 1000 includes a conductor 1100 thatis floating in that the gel material forming the member 270 completelysurrounds the conductor 1100. In one exemplary embodiment, the conductor1100 is a thin metal sheet plate that is disposed within the conductor1100. As will be appreciated, if a conductor, such as the plate 1100, isplaced in a homogeneous electric field, normal to the lines of theelectric field, the conductor 1100 practically has no effect on thefield (except that the two opposing faces of the conductor 1100 areequipotential and the corresponding equipotentials are slightlyshifted). Conversely, if the conductor 1100 is disposed parallel to theelectric field, there is a significant distortion of the electric field.The area in the immediate proximity of the conductor 1100 is notequipotential, in contrast to the situation where there is no conductor1100 present. When the conductor 1100 is disposed within the gel member270, the conductor 1100 will typically not effect the electric field (TCfield) for the reasons discussed above, namely that the conductor 1100is normal to the lines of the electric field.

[0123] If there is a breakdown of the external insulation 260 of theinsulated electrode 230, there is a strong current flow-current densityat the point of breakdown as previously discussed; however, the presenceof the conductor 1100 causes the current to spread throughout theconductor 1100 and then exit from the whole surface of the conductor1100 so that the current reaches the body 1000 with a current densitythat is neither high nor low. Thus, the current that reaches the skinwill not cause discomfort to the patient even when there has been abreakdown in the insulation 260 of the insulated electrode 230. It isimportant that the conductor 1100 is not grounded as this would cause itto abolish the electric field beyond it. Thus, the conductor 1100 is“floating” within the gel member 270.

[0124] If the conductor 1100 is introduced into the body tissues 1000and is not disposed parallel to the electric field, the conductor 1100will cause distortion of the electric field. The distortion can causespreading of the lines of force (low field density-intensity) orconcentration of the lines of field (higher density) of the electricfield, according to the particular geometries of the insert and itssurroundings, and thus, the conductor 1100 can exhibit, for example, ascreening effect. Thus, for example, if the conductor 1100 completelyencircles an organ 1101, the electric field in the organ itself will bezero since this type of arrangement is a Faraday cage. However, becauseit is impractical for a conductor to be disposed completely around anorgan, a conductive net or similar structure can be used to cover,completely or partially, the organ, thereby resulting in the electricfield in the organ itself being zero or about zero. For example, a netcan be made of a number of conductive wires that are arranged relativeto one another to form the net or a set of wires can be arranged tosubstantially encircle or otherwise cover the organ 1101. Conversely, anorgan 1103 to be treated (the target organ) is not covered with a memberhaving a Faraday cage effect but rather is disposed in the electricfield 1010 (TC fields).

[0125]FIG. 24 illustrates an embodiment where the conductor 1100 isdisposed within the body (i.e., under the skin) and it is located near atarget (e.g., a target organ). By placing the conductor 1100 near thetarget, high field density (of the TC fields) is realized at the target.At the same time, another nearby organ can be protected by disposing theabove described protective conductive net or the like around this nearbyorgan so as to protect this organ from the fields. By positioning theconductor 1100 in close proximity to the target, a high field densitycondition can be provided near or at the target. In other words, theconductor 1100 permits the TC fields to be focused at a particular area(i.e., a target).

[0126] It will also be appreciated that in the embodiment of FIG. 24,the gel members 260 can each include a conductor as described withreference to FIG. 23. In such an arrangement, the conductor in the gelmember 260 protects the skin surface (tissues) from any side effectsthat may be realized if a breakdown in the insulation of the insulatedelectrode 230 occurs. At the same time, the conductor 1100 creates ahigh field density near the target.

[0127] There are a number of different ways to tailor the field densityof the electric field by constructing the electrodes differently and/orby strategically placing the electrodes relative to one another. Forexample, in FIG. 25, a first insulated electrode 1200 and a secondinsulated electrode 1210 are provided and are disposed about a body1300. Each insulated electrode includes a conductor that is preferablysurrounded by an insulating material, thus the term “insulatedelectrode”. Between each of the first and second electrodes 1200, 1210and the body 1300, the conductive gel member 270 is provided. Electricfield lines are generally indicated at 1220 for this type ofarrangement. In this embodiment, the first insulated electrode 1200 hasdimensions that are significantly greater than the dimensions of thesecond insulated electrode 1210 (the conductive gel member for thesecond insulated electrode 1210 will likewise be smaller).

[0128] By varying the dimensions of the insulated electrodes, thepattern of the electric field lines 1220 is varied. More specifically,the electric field tapers inwardly toward the second insulated electrode1210 due to the smaller dimensions of the second insulated electrode1210. An area of high field density, generally indicated at 1230, formsnear the interface between the gel member 270 associated with the secondinsulated electrode 1210 and the skin surface. The various components ofthe system are manipulated so that the tumor within the skin or on theskin is within this high field density so that the area to be treated(the target) is exposed to electric field lines of a higher fielddensity.

[0129]FIG. 26 also illustrates a tapering TC field when a conductor 1400(e.g., a conductive plate) is disposed in each of the conductive gelmembers 270. In this embodiment, the size of the gel members 270 and thesize of the conductors 1400 are the same or about the same despite thedifferences in the sizes of the insulated electrodes 1200, 1210. Theconductors 1400 again can be characterized as “floating plates” sinceeach conductor 1400 is surrounded by the material that forms the gelmember 270. As shown in FIG. 26, the placement of one conductor 1400near the insulated electrode 1210 that is smaller than the otherinsulated electrode 1200 and is also smaller than the conductor 1400itself and the other insulated electrode 1200 is disposed at a distancetherefrom, the one conductor 1400 causes a decrease in the field densityin the tissues disposed between the one conductor 1400 and the otherinsulated electrode 1200. The decrease in the field density is generallyindicated at 1410. At the same time, a very inhomogeneous taperingfield, generally indicated at 1420, changing from very low density tovery high density is formed between the one conductor 1400 and theinsulated electrode 1210. One benefit of this exemplary configuration isthat it permits the size of the insulated electrode to be reducedwithout causing an increase in the nearby field density. This can beimportant since electrodes that having very high dielectric constantinsulation can be very expensive. For example, one insulated electrodecan cost $500.00 or more and further, the price is sensitive to theparticular area of treatment. Thus, a reduction in the size of theinsulated electrodes directly leads to a reduction in cost.

[0130] While the invention has been particularly shown and describedwith reference to preferred embodiments thereof, it will be understoodby those skilled in the art that various changes in form and details canbe made without departing from the spirit and scope of the invention.

What is claimed is:
 1. An apparatus for selectively destroying dividingcells in a target area of living tissue, the dividing cells havingpolarizable or polar or charged intracellular members, the apparatuscomprising: a first insulated electrode having a first conductor; asecond insulated electrode having a second conductor; an electric fieldsource connected to the first and second insulated electrodes forapplying an alternating electric potential difference across the firstand second conductors to create a condition in the dividing cells thatencourages the destruction thereof; an intervening member formed of afiller material disposed between one of the first and second insulatedelectrodes and a skin surface, the filler material having a highconductance; and a third conductor disposed within the interveningmember such that the filler material of the intervening membercompletely surrounds the third conductor.
 2. The apparatus of claim 1,wherein passage of the electric field through the dividing cells in lateanaphase or telophase transforms the electric field into anon-homogenous electric field that produces an increased densityelectric field in a region of a cleavage furrow of the dividing cells,the non-homogeneous electric field produced within the dividing cellsbeing of sufficient intensity to move the polarizable, polar or chargedintracellular members toward the cleavage.
 3. The apparatus of claim 1,wherein the third conductor disposed within the intervening membercomprises a flat conductor plate.
 4. The apparatus of claim 1, wherein alength of the third conductor is equal to or about equal to a length ofeach of the first and second conductors.
 5. The apparatus of claim 1,wherein the electric field is of sufficient frequency so that thenon-homogeneous electric field produced in the dividing cells defineselectric field lines which generally converge at a region of thecleavage furrow, thereby defining the increased density electric field,resulting in destruction of the dividing cells as a result of thepolarizable intracellular members movement toward the cleavage furrow.6. The apparatus of claim 1, further including: a first conductive leadoperatively connecting the first electrode to the electric field source;and a second conductive lead operatively connecting the second electrodeto the electric field source.
 7. The apparatus of claim 1, wherein thefirst electrode includes a first dielectric member that is in contactwith the first conductor, the first dielectric member for placementagainst the living tissue to form a capacitor and wherein the secondelectrode includes a second dielectric member that is in contact withthe second conductor, the second dielectric member for placement againstthe living tissue to form a capacitor.
 8. The apparatus of claim 1,wherein the alternating electric potential has a frequency of betweenabout 50 KHz to about 500 KHz.
 9. The apparatus of claim 1, wherein thealternating electric potential has a frequency of between about 100 KHzto about 300 KHz.
 10. The apparatus of claim 1, wherein the electricfield is a substantially uniform electric field prior to passing throughthe dividing cells.
 11. The apparatus of claim 1, wherein the electricfield source comprises a generator that generates an alternating voltagewaveform at frequencies between about 50 KHz to about 500 KHz.
 12. Theapparatus of claim 11, wherein each of the first and second electrodesare activated by the alternating voltage waveform.
 13. The apparatus ofclaim 1, wherein the first insulated electrode is of a first size andthe second insulated electrode is of a second size that is greater thanthe first size, the intervening member associated with the firstinsulated electrode being of a smaller size than the intervening memberassociated with the second insulated electrode.
 14. The apparatus ofclaim 13, wherein the electric field near the first insulated electrodeis of a higher field density than the electric field in other locationsbetween the first and second insulated electrodes.
 15. The apparatus ofclaim 14, wherein the electric field tapers inwardly to the firstinsulated electrode.
 16. The apparatus of claim 1, wherein theintervening filler comprises a gel formed of at least one materialselected from the group consisting of hydrogels, gelatins and agar. 17.The apparatus of claim 16, wherein the gel includes salt dissolvedtherein to increase the conductivity of the gel.
 18. An apparatus forselectively destroying dividing cells in a target area of living tissue,the dividing cells having polarizable or polar or charged intracellularmembers, the apparatus comprising: a first insulated electrode having afirst conductor; a second insulated electrode having a second conductor;an electric field source connected to the first and second insulatedelectrodes for applying an alternating electric potential differenceacross the first and second conductors to create a condition in thedividing cells that encourages the destruction thereof; an interveningmember disposed between one of the first and second insulated electrodesand a skin surface, the intervening member being formed of a fillermaterial that has a high conductance and a high dielectric constant; andwherein the first insulated electrode is of a first size and the secondinsulated electrode is of a second size that is greater than the firstsize, the intervening member associated with the first insulatedelectrode being of a smaller size than the intervening member associatedwith the second insulated electrode, resulting in the electric fieldnear the first insulated electrode being of a higher field density thanthe electric field in other locations between the first and secondinsulated electrodes.
 19. The apparatus of claim 18, wherein theelectric field tapers inwardly to the first insulated electrode.
 20. Theapparatus of claim 18, wherein the first electrode includes a firstdielectric member that is in contact with the first conductor, the firstdielectric member for placement against the living tissue to form acapacitor and wherein the second electrode includes a second dielectricmember that is in contact with the second conductor, the seconddielectric member for placement against the living tissue to form acapacitor.
 21. The apparatus of claim 18, wherein the alternatingelectric potential has a frequency of between about 50 KHz to about 500KHz.
 22. The apparatus of claim 18, wherein the alternating electricpotential has a frequency of between about 100 KHz to about 300 KHz. 23.The apparatus of claim 18, wherein the electric field is a substantiallyuniform electric field prior to passing through the dividing cells. 24.The apparatus of claim 18, wherein the electric field source comprises agenerator that generates an alternating voltage waveform at frequenciesbetween about 50 KHz to about 500 KHz.
 25. The apparatus of claim 18,wherein the intervening filler comprises a gel formed of at least onematerial selected from the group consisting of hydrogels, gelatins andagar.
 26. The apparatus of claim 25, wherein the gel includes saltdissolved therein to increase the conductivity of the gel.
 27. Anapparatus for selectively destroying dividing cells in a target area ofliving tissue, the dividing cells having polarizable or polar or chargedintracellular members, the apparatus comprising: a first insulatedelectrode having a first conductor; a second insulated electrode havinga second conductor; an electric field source connected to the first andsecond insulated electrodes for applying an alternating electricpotential difference across the first and second conductors to create acondition in the dividing cells that encourages the destruction thereof;an intervening member disposed each of the first and second insulatedelectrodes and a skin surface, each intervening member being formed of afiller material having a high conductance and a high dielectricconstant; and a third conductor disposed within the living tissue inclose proximity to the target area and between the first and secondinsulated electrodes, the third conductor causing increased electricfield density in the target area.
 28. The apparatus of claim 27, furtherincluding: a conductor protective member that is disposed around anorgan to be shielded and protected from effects of an electric fieldgenerated by the electric field source.
 29. The apparatus of claim 28,wherein the conductive protective member comprises a net formed ofconductive elements that is disposed around at least a portion of theorgan to be protected.
 30. The apparatus of claim 27, wherein eachinsulated electrode includes a conductor and a dielectric member incontact therewith and for placement against the living tissue to form acapacitor.
 31. The apparatus of claim 27, wherein the intervening fillercomprises a gel formed of at least one material selected from the groupconsisting of hydrogels, gelatins and agar.
 32. The apparatus of claim31, wherein the gel includes salt dissolved therein to increase theconductivity of the gel.